Proteomic profiling of kidney biopsies in nephrotic syndrome.

Background: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are patterns of kidney injury observed in the filtering units of the kidney known as glomeruli. These histological patterns are seen in kidney biopsies from individuals with idiopathic nephrotic syndrome (iNS), which occurs in both children and adults. However, there is some indication that MCD and FSGS are within the same phenotypic spectrum. Methods: From the NURTuRE cohort of individuals with NS, we performed laser microdissection and mass spectrometry analysis of kidney biopsy samples to identify proteomic patterns of disease. 56 individuals with iNS segregated by histological pattern (37 MCD and 19 FSGS) across three age groups: early childhood (0-6 years), late childhood (6-18 years) and adult (>18 years). Results: We found no distinct clustering of proteomic profiles between MCD and FSGS, but identified global differences in glomerular cell and extracellular matrix composition related to both histological pattern and age. The proteomic data are available via ProteomeXchange with identifier PXD053362. Conclusions: The lack of distinct clustering between MCD and FSGS in our study suggests shared biological processes between these injury patterns of iNS, supporting the hypothesis that they are part of the same disease spectrum. The global differences observed in glomerular cell and extracellular matrix composition suggest involvement of diverse biogeological processes as different patterns of iNS manifests in different age groups. This study also demonstrates the feasibility of pooling bioresources, central processing of heterogeneous tissue samples, and developing laser-microdissection and proteomic analysis methodology.